Corrigendum: tracing the origins of the Pituitary Adenylate-Cyclase Activating Polypeptide (PACAP)

A Corrigendum on Tracing the Origins of the Pituitary Adenylate-Cyclase Activating Polypeptide (PACAP) by Cardoso, J. C. R., Garcia, M. G., and Power, D. M. (2020). Front. Neurosci. 14:366. doi: 10.3389/fnins.2020.00366 In the original article, there was amistake in the legend for Table 1 as published. The table describes nomenclature for both vertebrates and non-vertebrates. In the original article, there was a mistake in Table 1 as published. PACAP receptor nomenclature for teleost and Actinopterygii (non-teleost) has errors. The Agnathan PACAP Receptor Gene/transcript should not be Adcyap1r1. During production, PACAP peptide column was erroneously positioned under the PACAP receptor. The corrected Table 1 and legend appears below. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.info:eu-repo/semantics/publishedVersio

Local Delivery of Therapeutics to the Inner Ear: The State of the Science

BACKGROUND: Advances in the understanding of the genetic and molecular etiologies of inner ear disorders have enabled the identification of therapeutic targets and innovative delivery approaches to the inner ear. As this field grows, the need for knowledge about effective delivery of therapeutics to the inner ear has become a priority. This review maps all clinical and pre-clinical research published in English in the field to date, to guide both researchers and clinicians about local drug delivery methods in the context of novel therapeutics. METHODS: A systematic search was conducted using customized strategies in Cochrane, pubmed and EMBASE databases from inception to 30/09/2018. Two researchers undertook study selection and data extraction independently. RESULTS: Our search returned 12,200 articles, of which 837 articles met the inclusion criteria. 679 were original research and 158 were reviews. There has been a steady increase in the numbers of publications related to inner ear therapeutics delivery over the last three decades, with a sharp rise over the last 2 years. The intra-tympanic route accounts for over 70% of published articles. Less than one third of published research directly assesses delivery efficacy, with most papers using clinical efficacy as a surrogate marker. CONCLUSION: Research into local therapeutic delivery to the inner ear has undergone a recent surge, improving our understanding of how novel therapeutics can be delivered. Direct assessment of delivery efficacy is challenging, especially in humans, and progress in this area is key to understanding how to make decisions about delivery of novel hearing therapeutics

A retrospective review of post-metamorphic mountain chicken frog (leptodactylus fallax) necropsy findings from European zoological collections, 1998 to 2018

The mountain chicken frog (Leptodactylus fallax) is the largest endemic amphibian species in the Western Hemisphere. Since 1998, this critically endangered species has been maintained as a European Endangered Species Programme, but low breeding success and a high mortality rate threaten the sustainability of the captive frog population. In the current study, we analyzed gross and histopathologic postmortem information from 212 mountain chicken frogs that died in European zoological collections from 1998 to 2018. Thin body condition was the most commonly reported finding across all submissions, observed in 125 frogs. The gastrointestinal and urinary systems were reported to have the highest prevalence of pathologic findings on gross and histopathologic examination. Inflammatory disease was the most frequent diagnosis after histopathologic examination of relevant tissues, with intestinal inflammatory disease (n = 76) followed by tubulointerstitial nephritis (n = 26) being the most commonly reported. Neoplasia was reported in 42 of 212 (19.8%) frogs, all of which were adults. A defined cause of death, or reason for euthanasia, was proposed for 164 of 212 (77.4%) frogs, with inflammatory diseases processes (74 of 212; 34.9%) most commonly implicated. Intestinal adenocarcinoma, seemingly restricted to the colon, caused the deaths of 31 adult frogs. Further investigations to determine factors contributing to the high incidence of inflammatory disease processes and neoplasia are advocated to improve the health and sustainability of the captive mountain chicken frog population

Development of a dynamic framework to explain population patterns of leisure-time physical activity through agent-based modeling.

Despite the increasing body of evidences on the factors influencing leisure-time physical activity, our understanding of the mechanisms and interactions that lead to the formation and evolution of population patterns is still limited. Moreover, most frameworks in this field fail to capture dynamic processes. Our aim was to create a dynamic conceptual model depicting the interaction between key psychological attributes of individuals and main aspects of the built and social environments in which they live. This conceptual model will inform and support the development of an agent-based model aimed to explore how population patterns of LTPA in adults may emerge from the dynamic interplay between psychological traits and built and social environments. We integrated existing theories and models as well as available empirical data (both from literature reviews), and expert opinions (based on a systematic expert assessment of an intermediary version of the model). The model explicitly presents intention as the proximal determinant of leisure-time physical activity, a relationship dynamically moderated by the built environment (access, quality, and available activities) - with the strength of the moderation varying as a function of the person's intention- and influenced both by the social environment (proximal network's and community's behavior) and the person's behavior. Our conceptual model is well supported by evidence and experts' opinions and will inform the design of our agent-based model, as well as data collection and analysis of future investigations on population patterns of leisure-time physical activity among adults

Early Trends in Cystatin C and Outcomes in Patients with Cirrhosis and Acute Kidney Injury

Background. Acute kidney injury (AKI) is a common and severe complication in patients with cirrhosis. Progression of AKI to a higher stage associates with increased mortality. Intervening early in AKI when renal dysfunction is worsening may improve outcomes. However, serum creatinine correlates poorly with glomerular filtration in patients with cirrhosis and fluctuations may mask progression early in the course of AKI. Cystatin C, a low-molecular-weight cysteine proteinase inhibitor, is a potentially more accurate marker of glomerular filtration. Methods. We conducted a prospective multicenter study in patients with cirrhosis comparing changes in cystatin and creatinine immediately following onset of AKI as predictors of a composite endpoint of dialysis or mortality. Results. Of 106 patients, 37 (35%) met the endpoint. Cystatin demonstrated less variability between samples than creatinine. Patients were stratified into four groups reflecting changes in creatinine and cystatin: both unchanged or decreased 38 (36%) (Scr−/CysC−); only cystatin increased 25 (24%) (Scr−/CysC+); only creatinine increased 15 (14%) (Scr+/CysC−); and both increased 28 (26%) (Scr+/CysC+). With Scr−/CysC− as the reference, in both instances where cystatin rose, Scr−/CysC+ and Scr+/CysC+, the primary outcome was significantly more frequent in multivariate analysis, and , respectively. However, when only creatinine rose, outcomes were similar to the reference group. Conclusions. Changes in cystatin levels early in AKI are more closely associated with eventual dialysis or mortality than creatinine and may allow more rapid identification of patients at risk for adverse outcomes

A Dataset and Baselines for Visual Question Answering on Art

Answering questions related to art pieces (paintings) is a difficult task, as it implies the understanding of not only the visual information that is shown in the picture, but also the contextual knowledge that is acquired through the study of the history of art. In this work, we introduce our first attempt towards building a new dataset, coined AQUA (Art QUestion Answering). The question-answer (QA) pairs are automatically generated using state-of-the-art question generation methods based on paintings and comments provided in an existing art understanding dataset. The QA pairs are cleansed by crowdsourcing workers with respect to their grammatical correctness, answerability, and answers' correctness. Our dataset inherently consists of visual (painting-based) and knowledge (comment-based) questions. We also present a two-branch model as baseline, where the visual and knowledge questions are handled independently. We extensively compare our baseline model against the state-of-the-art models for question answering, and we provide a comprehensive study about the challenges and potential future directions for visual question answering on art

Building Conventional Metasurfaces with Unconventional Interband Plasmonics: A Versatile Route for Sustainable Structural Color Generation Based on Bismuth

This is the final version. Available on open access from Wiley via the DOI in this recordData Availability Statement: The data that support the findings of this study are available in the supplementary material of this article.Plasmonic metasurfaces for structural color generation are typically built using the archetypal noble metals, gold, and silver. These possess plasmonic properties in the visible spectrum due to their inherent high free carrier densities. However, they are much more expensive compared to many other metals and exhibit several nanofabrication issues such as bad surface adhesion or thermally activated inter-diffusion. In this work, it is shown that interband plasmonic materials –whose optical properties are driven by interband transitions instead of free carriers— are appealing candidates for the fabrication of sustainable and cost-efficient metasurfaces for structural coloring. By using bismuth, an environment-friendly interband plasmonic material cheaper than gold and silver, nanodisks gap-plasmon metasurfaces and planar Fabry-Perot cavities are modeled and fabricated, which both successfully enable pure colors that can be robustly tailored upon suitable design. By direct experimental comparison between both types of design in terms of color efficiency, fabrication complexity, and angular robustness; how bismuth-based gap surface plasmon metasurfaces can be excellent candidates for color microprinting is shown, whereas nanolayered Bi Fabry-Pérot cavities are ideal for macroscopic color coatings due to their ease of fabrication and implementation.European CommissionAgencia Estatal de InvestigaciónMinisterio de Ciencia e Innovació

Statin Induced Myopathy and Myalgia: Time Trend Analysis and Comparison of Risk Associated with Statin Class from 1991–2006

BACKGROUND: Statins are widely used as a cholesterol lowering medication, reduce cardiovascular mortality and morbidity in high risk patients; and only rarely cause serious adverse drug reactions (ADRs). UK primary care databases of morbidity and prescription data, which now cover several million people, have potential for more powerful analytical approaches to study ADRs including adjusting for confounders and examining temporal effects. METHODS: Case-crossover design in detecting statin associated myopathy ADR in 93, 831 patients, using two independent primary care databases (1991-2006). We analysed risk by drug class, by disease code and cumulative year, exploring different cut-off exposure times and confounding by temporality. RESULTS: Using a 12 and 26 week exposure period, large risk ratios (RR) are associated with all classes of statins and fibrates for myopathy: RR 10.6 (9.8-11.4) and 19.9 (17.6-22.6) respectively. At 26 weeks, the largest risks are with fluvastatin RR 33.3 (95% CI 16.8-66.0) and ciprofibrate (with previous statin use) RR 40.5 (95% CI 13.4-122.0). AT 12 weeks the differences between cerivastatin and atorvastatin RR for myopathy were found to be significant, RR 2.05 (95% CI 1.2-3.5), and for rosuvastatin and fluvastatin RR 3.0 (95% CI 1.6-5.7). After 12 months of statin initiation, the relative risk for myopathy for all statins and fibrates increased to 25.7 (95% CI 21.8-30.3). Furthermore, this signal was detected within 2 years of first events being recorded. Our data suggests an annual incidence of statin induced myopathy or myalgia of around 11.4 for 16, 591 patients or 689 per million per year. CONCLUSION: There may be differential risks associated with some classes of statin and fibrate. Myopathy related to statin or fibrate use may persist after a long exposure time (12 months or more). These methods could be applied for early detection of harmful drug side effects, using similar primary care diagnostic and prescribing data

Exceptionally large migration length of carbon and topographically-facilitated self-limiting molecular beam epitaxial growth of graphene on hexagonal boron nitride

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Available online 18 December 2016We demonstrate growth of single-layer graphene (SLG) on hexagonal boron nitride (h-BN) by molecular beam epitaxy (MBE), only limited in area by the finite size of the h-BN flakes. Using atomic force microscopy and micro-Raman spectroscopy, we show that for growth over a wide range of temperatures (500◦C – 1000◦C) the deposited carbon atoms spill off the edge of the h-BN flakes. We attribute this spillage to the very high mobility of the carbon atoms on the BN basal plane, consistent with van der Waals MBE. The h-BN flakes vary in size from 30 µm to 100 µm, thus demonstrating that the migration length of carbon atoms on h-BN is greater than 100 µm. When sufficient carbon is supplied to compensate for this loss, which is largely due to this fast migration of the carbon atoms to and off the edges of the h-BN flake, we find that the best growth temperature for MBE SLG on h-BN is ∼950◦C. Self-limiting graphene growth appears to be facilitated by topographic h-BN surface features: We have thereby grown MBE self-limited SLG on an h-BN ridge. This opens up future avenues for precisely tailored fabrication of nano- and hetero-structures on pre-patterned h-BN surfaces for device applications.This work is supported by ONR (N000140610138 and Graphene MURI), AFOSR (FA9550-11-1-0010), EFRC Center for Re-Defining Photovoltaic Efficiency through Molecule Scale Control (award DE-SC0001085), NSF (CHE-0641523), NYSTAR and Spanish Government (AIC-B-2011-0806, MAT2014-54231, MAT2015-67021-R). S.W. and A.P. were supported by the US Department of Energy Office of Science, Division of Materials Science and Engineering (award DE-SC0010695)

Astrocytes display cell autonomous and diverse early reactive states in familial amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a rapidly progressive and fatal disease. Although astrocytes are increasingly recognized contributors to the underlying pathogenesis, the cellular autonomy and uniformity of astrocyte reactive transformation in different genetic forms of amyotrophic lateral sclerosis remain unresolved. Here we systematically examine these issues by using highly enriched and human induced pluripotent stem cell-derived astrocytes from patients with VCP and SOD1 mutations. We show that VCP mutant astrocytes undergo cell-autonomous reactive transformation characterized by increased expression of complement component 3 (C3) in addition to several characteristic gene expression changes. We then demonstrate that isochronic SOD1 mutant astrocytes also undergo a cell-autonomous reactive transformation, but that this is molecularly distinct from VCP mutant astrocytes. This is shown through transcriptome-wide analyses, identifying divergent gene expression profiles and activation of different key transcription factors in SOD1 and VCP mutant human induced pluripotent stem cell-derived astrocytes. Finally, we show functional differences in the basal cytokine secretome between VCP and SOD1 mutant human induced pluripotent stem cell-derived astrocytes. Our data therefore reveal that reactive transformation can occur cell autonomously in human amyotrophic lateral sclerosis astrocytes and with a striking degree of early molecular and functional heterogeneity when comparing different disease-causing mutations. These insights may be important when considering astrocyte reactivity as a putative therapeutic target in familial amyotrophic lateral sclerosis